دورية أكاديمية
أعرض في EDS

Targeted delivery of type I TGF-β receptor-mimicking peptide to fibrotic kidney for improving kidney fibrosis therapy via enhancing the inhibition of TGF-β1/Smad and p38 MAPK pathways.

التفاصيل البيبلوغرافية
العنوان: Targeted delivery of type I TGF-β receptor-mimicking peptide to fibrotic kidney for improving kidney fibrosis therapy via enhancing the inhibition of TGF-β1/Smad and p38 MAPK pathways.
المؤلفون: Wang X; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China; Laboratory of Pathogenic Microbiology and Immunology, Mudanjiang Medical University, Mudanjiang 157011, PR China; Department of Cell Biology, Mudanjiang Medical University, Mudanjiang 157011, PR China., Liu X; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China., Xu L; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China., Li Y; Laboratory of Pathogenic Microbiology and Immunology, Mudanjiang Medical University, Mudanjiang 157011, PR China., Zheng B; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China., Xia C; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China., Wang J; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China., Liu H; Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, PR China; Laboratory of Pathogenic Microbiology and Immunology, Mudanjiang Medical University, Mudanjiang 157011, PR China. Electronic address: liuhaifeng@mdjmu.edu.cn.
المصدر: International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112483. Date of Electronic Publication: 2024 Jun 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
مواضيع طبية MeSH: Fibrosis*/drug therapy , Transforming Growth Factor beta1*/metabolism , p38 Mitogen-Activated Protein Kinases*/metabolism , Kidney*/pathology , Kidney*/drug effects , Kidney*/metabolism , Mice, Inbred C57BL* , Smad Proteins*/metabolism, Animals ; Mice ; NIH 3T3 Cells ; Male ; Signal Transduction/drug effects ; Myofibroblasts/drug effects ; Myofibroblasts/metabolism ; Peptides/therapeutic use ; Peptides/pharmacology ; Kidney Diseases/drug therapy ; Kidney Diseases/pathology ; Kidney Diseases/metabolism ; Receptor, Transforming Growth Factor-beta Type I/metabolism ; Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors ; Humans ; Disease Models, Animal ; Cell Proliferation/drug effects
مستخلص: Renal fibrosis is a representative pathological feature of various chronic kidney diseases, and efficient treatment is needed. Interstitial myofibroblasts are a key driver of kidney fibrosis, which is dependent on the binding of TGF-β1 to type I TGF-β receptor (TβRI) and TGF-β1-related signaling pathways. Therefore, attenuating TGF-β1 activity by competing with TGF-β1 in myofibroblasts is an ideal strategy for treating kidney fibrosis. Recently, a novel TβRI-mimicking peptide RIPΔ demonstrated a high affinity for TGF-β1. Thus, it could be speculated that RIPΔ may be used for anti-fibrosis therapy. Platelet-derived growth factor β receptor (PDGFβR) is highly expressed in fibrotic kidney. In this study, we found that target peptide Z-RIPΔ, which is RIPΔ modified with PDGFβR-specific affibody Z PDGFβR , was specifically and highly taken up by TGF-β1-activated NIH3T3 fibroblasts. Moreover, Z-RIPΔ effectively inhibited the myofibroblast proliferation, migration and fibrosis response in vitro. In vivo and ex vivo experiments showed that Z-RIPΔ specifically targeted fibrotic kidney, improved the damaged renal function, and ameliorated kidney histopathology and renal fibrosis in UUO mice. Mechanistic studies showed that Z-RIPΔ hold the stronger inhibition of the TGF-β1/Smad and TGF-β1/p38 pathways than unmodified RIPΔ in vitro and in vivo. Furthermore, systemic administration of Z-RIPΔ to UUO mice led to minimal toxicity to major organs. Taken together, RIPΔ modified with Z PDGFβR increased its therapeutic efficacy and reduced its systemic toxicity, making it a potential candidate for targeted therapy for kidney fibrosis.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Affibody; Myofibroblasts; Platelet-derived growth factor β receptor; Renal fibrosis; Type I TGF-β receptor
المشرفين على المادة: 0 (Transforming Growth Factor beta1)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
0 (Smad Proteins)
0 (Peptides)
EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
تواريخ الأحداث: Date Created: 20240616 Date Completed: 20240710 Latest Revision: 20240710
رمز التحديث: 20240710
DOI: 10.1016/j.intimp.2024.112483
PMID: 38880023
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-1705
DOI:10.1016/j.intimp.2024.112483